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PMID: 18081695 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Pseudomonas aeruginosa Type III secretion system plays a dual role in the regulation of caspase-1 mediated IL-1beta maturation.

Journal of cellular and molecular medicine ·Vol. 12 ·No. 5A ·2008-00-00 ·Pages 1767-76

Galle M, Schotte P, Haegman M, Wullaert A, Yang HJ, Jin S, Beyaert R

Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that forms a serious problem for immunocompromised patients and also the leading cause of mortality in cystic fibrosis. The overall importance of a functional Type III secretion system (T3SS) in P. aeruginosa virulence has been well established, but the underlying mechanisms are still unclear. Using in vitro infected macrophages as w as a murine model of acute lung infection, we show that the Caspase-1 mediated maturation and secretion of IL-1beta needs a translocation competent T3SS and Flagellin, but not the Type III effector proteins ExoS, ExoT and ExoY. However, ExoS was found to negative regulate the P. aeruginosa induced IL-1beta maturation by a mechanism that is dependent on its ADP ribosyltransferase activity. Moreov ExoS deficiency also switched the mode of macrophage death from apoptosis to pro-inflammatory pyroptosis. Altogether, these data demonstrate a dual role for the P. aeruginosa T3SS in the regulation of Caspase-1 mediated IL-1beta production and provide new insights into the mechanisms of immune evasion by this pathogen.

MeSH Terms
ADP Ribose Transferases/metabolism Animals Apoptosis Bacterial Toxins/metabolism Caspase 1/metabolism Cells, Cultured Female Interleukin-1beta/metabolism Macrophages/cytology,metabolism Mice Mice, Inbred DBA Pseudomonas Infections/genetics,metabolism,pathology Pseudomonas aeruginosa/metabolism
Chemicals
Bacterial Toxins Interleukin-1beta ADP Ribose Transferases exoenzyme S Caspase 1
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Galle M
Department of Molecular Biology, Ghent University, Ghent, Belgium.
Schotte P
Haegman M
Wullaert A
Yang H J
Jin S
Beyaert R
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Article Info
Journal
Journal of cellular and molecular medicine
Abbr.
J Cell Mol Med
ISSN
1582-1838
DOI
10.1111/j.1582-4934.2007.00190.x
Published
2008-00-00
Epub
2007-00-10
Pages
1767-76
Language
English
Region
England
NLM ID
101083777
PMCID
PMC3918092
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1582-4934.2007.00190.x PMC Full Text View journal details
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